Chlorination of hydroxyethyl cellulose enables selective functionalization

Chemical modification of cellulose is challenging due to its low reactivity and poor solubility. Halogenation followed by displacement reactions has been demonstrated to be a valuable strategy for appending new functionalities to the anhydroglucose rings of cellulose and cellulose derivatives. In this paper, we report a simple and efficient pathway to modify the inexpensive, commercial cellulose ether, hydroxyethyl cellulose (HEC). First, methanesulfonyl chloride (MsCl) in N, N-dimethyl formamide (DMF) can selectively chlorinate the terminal primary hydroxyl groups from hydroxyethyl cellulose (HEC), thereby affording high terminal chloride content. Then, the resulting chlorinated HEC undergoes displacement reactions with various nucleophiles including azide (NaN₃), amine (1-methylimidazole), and thiols (3-mercaptopropionic acid and 2-mercaptoethanol). All products were characterized by NMR and FT-IR spectroscopic methods. Exploiting this strategy, we prepared a library of HEC derivatives, including cationic and anionic derivatives, which are of great interest in various applications including as surfactants, in gas separation membranes, and as crystallization inhibitors in amorphous solid dispersions for oral drug bioavailability enhancement.